1. Field of the Invention
The present invention relates to a polypeptide and fragments thereof which induce interferon-γ (IFN-γ) production by immunocompetent cells, a pharmaceutical composition containing same, and a monoclonal antibody specific for this polypeptide. The present invention also relates to a DNA encoding the IFN-γ production inducing polypeptide or peptide, methods of using the polypeptide or fragments thereof, pharmaceutical compositions, or monoclonal antibodies.
2. Description of the Related Art
Interferon-γ (IFN-γ) is a protein which is known to have antiviral, antioncotic, and immunoregulatory activities, and which is produced by immunocompetent cells stimulated with antigens or mitogens. Because of these biological activities, IFN-γ was expected to be used as an antitumor agent and was tested in clinical trials as a therapeutic for treating malignant tumors in general, including brain tumors. IFN-γ preparations, which are now commercially available, are roughly classified into two groups, natural IFN-γ polypeptides produced by immunocompetent cells and recombinant IFN-γ polypeptides produced in Escherichia coli transformed with a DNA which encodes for natural IFN-γ. In the clinical trials, either natural IFN-γ polypeptide or recombinant IFN-γ is administered to patients as an exogenous IFN-γ.
Natural IFN-γ polypeptides are usually produced by culturing established immunocompetent cells in nutrient culture media supplemented with IFN-γ inducers to produce IFN-γ polypeptides, and then purifying the produced IFN-γ polypeptides. It is known that the type of IFN-γ inducer used in the nutrient culture media greatly influences the production yield of IFN-γ polypeptide as well as the ease of IFN-γ purification and the safety of the final IFN-γ preparations. Generally, mitogens such as concanavalin A (Con A), lentil lectin from Lens culinaris, pokeweed pectin from Phytolacca americana, endotoxin and lipopolysaccharide can be used as IFN-γ inducers. However, these mitogens have problems with the molecular variety and quality of the preparation, which depend on the origin of the mitogen and purification methods used, as well as on production of mitogens with constant IFN-γ inducibility in satisfactory yields. In addition, most of these mitogens induce unfavorable side effects when administered in vivo, with some even showing toxicity. As a result, it is not practical to use such mitogens to induce IFN-γ production by direct in vivo administration to a patient.
Recently, some pharmaceuticals which contain as an effective ingredient a cytokine, such as interferon-α, interferon-β, TNF-α, TNF-β, interleukin 2, and interleukin 12, as well as IFN-γ, were developed or are being explored for actual use. These pharmaceuticals can be used as an antitumor agent, antiviral agent, antiseptic or immunoregulatory agent and, if necessary, they can be used together with other medicaments.
Unlike chemically-synthesized pharmaceuticals, the aforesaid pharmaceuticals have the characteristic that they can be administered to patients for a relatively long period of time without inducing serious side effects. However, they also have the drawback that their therapeutic effects are relatively low, and they cannot substantially abate or cure diseases when used alone; the results vary depending on the types of diseases and symptoms to be treated. Accordingly, these pharmaceuticals are now used as a supplement to chemically-synthesized agents in the treatment of serious diseases, such as malignant tumors, to prolong the patient's life.